INVESTIGADORES
RODENAK KLADNIEW Boris Emilio
congresos y reuniones científicas
Título:
Modulation of the mevalonate pathway and cell growthby linalool in hepatocellular carcinoma cells
Autor/es:
RODENAK KLADNIEW B; GALLE M; CASTRO A; MONTERO VILLEGAS S; DE SAEGER C; STÄRKEL, P; CRESPO R; POLO M; GARCÍA DE BRAVO M
Lugar:
Puerto Iguazú
Reunión:
Conferencia; 56th International Conference on the Bioscience of lipids; 2015
Institución organizadora:
International Conference on the Bioscience of lipids
Resumen:
Linalool(LN)isamonoterpene-10carbonsisoprenoid-foundinessentialoilsofmanyaromaticplants.Themevalonatepathway(MP)hasbeenreportedasabranchedmetabolicpathwaymodulatedbyisoprenoids.Inadditiontocholesterol,thispathwayprovidesseveralothermoleculesrelevanttocellularmetabolism,suchasfarnesylpyrophosphateandgeranyl?geranylpyrophosphate,essentialintheprenylationofsmallGTPaseRas,amembraneanchoredproteinwhichplaysacriticalroleinsurvivalandcellproliferation.Therate-limitingenzymeoftheMPis3-hydroxy-3-methylglutarylcoenzyme-Areductase(HMGCR).WehavepreviouslydemonstratedthatLNisabletoinhibitcellgrowthandcholesterogenesisinhumanhepatocellularcarcinoma(HepG2)cells,thelatterasaconsequenceoftheinhibitionexertedbylinaloolatHMGCRlevelandsubsequentstepsspecificallycommittedtocholesterolsynthesis.TheaimofthisworkwastoelucidatethemechanismsinvolvedintheantiproliferativeeffectsexertedbyLNinHepG2cells.Forthispurposecellviabilityandproliferation(WST-1andBrdUincorporation),apoptosis(TUNEL,caspase-3activity),cellcycleanalysis(flowcytometry),exogenousmevalonateaditionandRassubcellularlocalizationwerestudied.OurresultsshowedthatLNarrestedcellcycleprogressioninG0/G1phase,inducedapoptosisanddiminishedRaslevelsinthemembranefraction.AddedexogenousmevalonatefailedtoreversetheinhibitionofproliferationexertedbyLN,proposingthatHMGCRinhibitionaloneisnotresponsiblefortheantiproliferativeactivityofthiscompoundandsuggestingthatRasinhibitioncouldberesponsible,atleastinpart,fortheantiproliferativeactivitypromotedbyLN.ThisinhibitioncouldtriggertheG0/G1arrestandtheinductionofapoptosis.ThisworkcontributestoaclearerunderstandingofthemechanismsofactionofLNsuggestingthatitsusecouldprovidesignificanthealthbenefitsasachemopreventiveand/orchemotherapeuticagent.
